The objectives of proposed research are to utilize immunological methods to study the pharmacology of narcotic analgesics and to investigate the effect of specific anti-sera on the biologic actions of drugs. Derivatives of morphine and other opioids will be prepared and chemically characterized. The compounds will be conjugated with bovine serum albumin and the conjugates used to immunize rabbits. The amount of antibody and a measure of its affinity will be determined using a modification of Farr's ammonium sulfate method to measure antigen-binding capacity. Specificity of antiserum reactivity will be evaluated by determining the ability of various unlabeled opioids to inhibit the binding of the opioid used for immunization. The antisera will be studied for their effect on the depressant action of morphine on electrically-induced contraction of guinea pig ileum and on drug-seeking behavior of monkeys. Other specific objectives are preparation of derivatives for conjugation with protein that will present various portions of the opioid molecule as immunizing haptens and preparation of solid immunoadsorbents by reacting opiods and derivatives with matrix materials such as agarose. Selective immunization combined with selective adsorption of resulting antisera will provide antibodies with a high affinity and a considerably restricted range of reactivity. Purified antibodies reactive with particular regions of drug molecules should provide specific assay methods for individual opioids. They will also provide more effective approaches for investigating pharmacologic mechanisms of drug action, for determining affinity of tissue receptors, and for studying drug distribution and placental transfer in man and experimental animals.